Safe administration of Crotalidae equine immune F(ab')2 antivenom in a patient who suffered anaphylaxis from Crotalidae polyvalent immune Fab antivenom.

Allergic reactions to Crotalidae polyvalent immune Fab and Crotalidae immune F(ab')2 are uncommon but potentially life-threatening. It is unknown whether cross-reactivity reactions exist between these two antivenoms. We report a case of a patient who suffered anaphylaxis from Crotalidae polyvalent immune Fab but subsequently was safely administered Crotalidae immune F(ab')2 after a presumed Agkistrodon contortix (copperhead) envenomation. This single case supports the safety of Crotalidae immune F(ab')2 administration in patients with a history of anaphylaxis to Crotalidae polyvalent immune Fab treatment.

Upper Extremity Crotalid Envenomation: A Review of Incidence and Recent Trends in Management of Snakebites.

PURPOSE: The goal of this study was to evaluate the recent trends in the management of upper extremity Crotalid envenomation in the state of Georgia, United States. METHODS: A retrospective review of the Georgia Poison Center database looking at the reported snakebites to the upper extremity between 2015 and 2020 was performed. Patient demographics, timing and location of injury, severity of envenomation, treatment, including use of antivenin and surgical intervention, and reported complications related to the use of antivenin was extracted. RESULTS: A retrospective review of snakebites between 2015 and 2020 showed 2408 snakebite cases with a mean patient age of 37.4 years. Males incurred 62.8% of all bites. The highest incidence was in summer 52.5%, and between the hours of 5 PM to midnight 57.2%. Overall, 1010 (41.9%) of all bites were categorized as venomous snakebites (55.6% copperhead, 20% rattlesnake, 2.4% cottonmouth, and 22% miscellaneous [including 3 Elapid envenomations] or unidentified. The total number of venomous bites to the upper extremity was 575 (56.9%) and 567 patients received antivenin. Envenomation severity was mild in 29%, moderate in 45%, severe in 10%, and undetermined in 16% of cases. Crotalidae polyvalent immune Fab (Ovine) was the main antivenin used, with overall mean initial therapy dose of 6.2 vials and 59% of patients receiving maintenance therapy. Three patients (0.5%) had a severe anaphylactic reaction to antivenin requiring cessation of therapy. Seven patients had acute compartment syndrome of the upper extremity requiring fasciotomy (3 copperhead, 2 rattlesnake, and 2 unidentified). There was no reported mortality during this period. CONCLUSIONS: Hand surgeons should be familiar with the management of upper extremity Crotalid envenomation. Antivenin remains the main treatment for symptomatic patients. Crotalid snakebites rarely require operative intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Intraspecific investigation of dehydration-enhanced innate immune performance and endocrine stress response to sublethal dehydration in a semi-aquatic species of pit viper.

Sublethal dehydration can cause negative physiological effects, but recent studies investigating the sub-lethal effects of dehydration on innate immune performance in reptiles have found a positive correlation between innate immune response and plasma osmolality. To investigate whether this is an adaptive trait that evolved in response to dehydration in populations inhabiting water-scarce environments, we sampled free-ranging cottonmouth snakes (n=26 adult cottonmouths) from two populations inhabiting contrasting environments in terms of water availability: Snake Key (n=12), an island with no permanent sources of fresh water, and Paynes Prairie (n=14), a flooded freshwater prairie. In addition to field surveys, we manipulated the hydration state of 17 cottonmouths (Paynes Prairie n=9, Snake Key n=8) in a laboratory setting and measured the response of corticosterone and innate immune performance to dehydration with the aim of identifying any correlation or trade-offs between them. We measured corticosterone of cottonmouths at a baseline level and then again following a 60 min stress test when at three hydration states: hydrated, dehydrated and rehydrated. We found that innate immune performance improved with dehydration and then returned to baseline levels within 48 h of rehydration, which agrees with previous research in reptiles. Despite the frequent exposure of cottonmouths on Snake Key to dehydrating conditions, we did not find cottonmouths inhabiting the island to show a greater magnitude or more prolonged immune response compared with cottonmouths from Paynes Prairie. We also found a positive association between dehydration and corticosterone values.

Epidemiology and Characteristics of North American Crotalid Bites Reported to the National Poison Data System 2006-2020.

OBJECTIVES: North American pit viper, or crotalid bites, remain a low-incidence and potentially high-consequence medical event. Although the venom of these snakes is known to cause tissue, hematologic, and neurologic toxicity, the published literature on North American crotalid bites remains limited. The National Poison Data System, the data repository for the 55 poison control centers in the United States, offers a unique opportunity to examine nationwide trends involving venomous snake bites. METHODS: National Poison Data System cases involving North American crotalids from 2006 to 2020 were analyzed. Data collected included age and type of snake, date, geographic location, pertinent clinical characteristics, treatments administered, and medical outcomes including incidence of "dry" bites and death. RESULTS: A total of 55,914 cases were identified during the 15-year study period. Cases, especially those involving copperheads, increased during the study period. Most of the cases were reported in July. Cases were reported in all 50 states and Washington, DC, with Texas having the most cases (n = 9115). North Carolina had the largest increase in bites during the study period. Moderate or major medical outcomes were documented in 58% (n = 32,584) of cases, with 25% (n = 14,195) being admitted to a critical care unit. Puncture wound, edema, and pain were the most commonly documented symptoms. Antivenom was documented as being administered in 25% (n = 14,151) of cases. Dry bites were reported in <1.5% of cases. Thirty-two deaths were reported, 23 involving rattlesnakes. CONCLUSIONS: This study demonstrates that reported North American crotalid bites appear to be increasing over time and are associated with potentially significant morbidity. Mortality, however, remains low.

Platelet Desialylation Is a Novel Mechanism and Therapeutic Target in Daboia siamensis and Agkistrodon halys Envenomation-Induced Thrombocytopenia.

Venom-induced thrombocytopenia (VIT) is one of the most important hemotoxic effects of a snakebite, which is often associated with venom-induced consumptive coagulopathy (VICC). Refractory thrombocytopenia without significant coagulation abnormalities has also been reported after envenomation by some viperid snakes; however, the mechanisms are not well understood and therapeutic strategies are lacking. Here, we found that patients injured by Daboia siamensis or Agkistrodon halys snakes, who were resistant to standard antivenom treatment, had developed coagulopathy-independent thrombocytopenia. Venoms from these viperid snakes, rather than from the elapid snake (Bungarus multicinctus), induced platelet surface expression of neuraminidase-1 (NEU-1), and significantly increased the desialylation of the glycoproteins on human platelets. The desialylated platelets caused by viperid snake venoms were further internalized by macrophages, which resulted in reduced platelet numbers in peripheral blood. Importantly, neuraminidase inhibitor significantly decreased viper venom-induced platelet desialylation, therefore inhibiting platelet phagocytosis by macrophages, and alleviating venom-induced thrombocytopenia. Collectively, these findings support an important role for desialylated platelet clearance in the progression of viper envenomation-induced, coagulopathy-independent thrombocytopenia. Our study demonstrates that the neuraminidase inhibitor may be a potential therapy or adjuvant therapy to treat snakebite-induced thrombocytopenia.

How Should Native Crotalid Envenomation Be Managed in the Emergency Department?

BACKGROUND: Pit vipers, also known as crotalids, are a group of snakes including rattlesnakes, copperheads, and cottonmouths (water moccasins). Crotalids have a broad geographic distribution across the United States, and bites from these snakes can carry significant morbidity. Their envenomations are characterized by local tissue effects, hematologic effects, and systemic effects. Envenomations are generally treated with 1 of 2 antivenoms available in the United States. OBJECTIVE: We developed a series of clinical questions to assist and guide the emergency physician in the acute management of a patient envenomated by a crotalid. METHODS: We conducted a PubMed literature review from January 1970 to May 2020 in English for articles with the keywords "bite" and "crotalidae." RESULTS: Our literature search resulted in 177 articles. A total of 33 articles met criteria for rigorous review and citation in the development of these consensus guidelines. CONCLUSIONS: Patients should be initially evaluated, stabilized, and assessed for local effects, hematologic effects, and systemic toxicity suggestive of envenomation. Antivenom should be given if toxic effects are present. Surgical intervention including debridement and fasciotomy should be avoided. Prophylactic antibiotics are not necessary.

No Change in the Use of Antivenom in Copperhead Snakebites in Ohio.

INTRODUCTION: Historically, copperhead snake (Agkistrodon contortrix) envenomations were not treated with antivenom owing to related adverse events and little benefit. However, recent studies have shown improved outcomes with antivenom use. We hypothesized that the frequency of antivenom use for copperhead envenomation in Ohio has increased as benefits of administration became more widely known. METHODS: All copperhead snakebites reported to the Ohio poison control centers from 2006 through 2016 were compiled. Antivenom use, bite severity, and disposition were abstracted. A nonparametric test for trend was used to evaluate changes over time for the number of patients treated with antivenom and patient disposition. Logistic regression was used to assess the odds of admission vs discharge with antivenom administration, bite severity, age, and sex as independent variables. RESULTS: Ninety-eight patients reported copperhead snakebites to the poison control centers. The test of trend showed no change in the proportion of patients treated with antivenom by year (P=0.42). There was no difference in the proportion of patients discharged home (P=0.38) per year. Logistic regression showed antivenom use was associated with an odds ratio for admission of 46.7 (95% CI: 7.3-296.4). CONCLUSIONS: The frequency of antivenom use for copperhead bites did not significantly increase between 2006 and 2016. Administration of antivenom was associated with a large increase in the odds of admission to the hospital, even when controlling for bite severity. Further education regarding the benefits and safety of antivenom may increase its use for copperhead snakebites, but may lead to an increase in hospital admissions.

[Effect of hemocoagulase agkistrodon on coagulation status in patients with traumatic brain injury in vitro].

Objective: To analyze the effects of hemocoagulase agkistrodon (HCA) on the coagulation status of healthy people and traumatic brain injury (TBI) patients in vitro. Methods: A total of 10 TBI patients were enrolled from December 2018 to June 2019,and 24 age and sex matched healthy controls were also enrolled. Clinical and pathological data, blood samples of all subjects were collected. Different gradient concentrations of HCA were added to the blood samples which were detected by thromboelastography, and the R value, K value, α angle and MA value of thromboelastography parameters between the two groups were analyzed to explore the effect of HCA on the coagulation status of patients with TBI. Results: With the increase of HCA concentration in blood samples, the R and K values gradually increased, and the α angles and MA values gradually decreased in both TBI patients group which included 7 males and 3 females, with an median age of 33 (28-39) years old and healthy control group which included 11 males and 13 females, with an median age of 33 (23-49) years old. The differences in the R values, K values, α angles, and MA values of different concentration gradients were statistically significant in both healthy control group and TBI patients group (χ2 were 109.80, 131.28, 185.47, 165.97 and 54.92, 75.60, 80.12, 59.25, respectively, all P<0.001). The differences between R values after adding HCA of 0-0.105 U/ml in the healthy group were statistically significant (P=0.025), but K values, α angles and MA values were not statistically significant (P values were 0.275, 0.206 and 0.330, respectively); the R values of the TBI patients group were not statistically significant after adding HCA of 0 to 0.105 U/ml (P=0.976), and the K values, α angles, and MA values were statistically significant (P values were 0.047, 0.041, and 0.034, respectively).The R values of the healthy control group, the TBI patients group, and the overall data were significantly positively correlated with the HCA dose (r values were 0.552、0.700、0.420, respectively, P<0.001), the K values were significantly positively correlated with the HCA dose (r values were 0.726、0.861、0.750, respectively, P<0.001), the α angles were significantly negatively correlated with the HCA dose (r values were -0.815、-0.876、-0.807, respectively, P<0.001) and the MA values were significantly negatively correlated with the HCA dose (r values were -0.757、-0.710、-0.729, respectively, P<0.001). Conclusions: HCA does not aggravate the procoagulant state of blood in healthy people and TBI patients, and with the increase of HCA concentration in blood, the blood samples of both groups show a tendency to decrease the coagulation ability.

Tipping the Scales: The Migration-Selection Balance Leans toward Selection in Snake Venoms.

The migration-selection interaction is the strongest determinant of whether a beneficial allele increases in frequency within a population. Results of empirical studies examining the role of gene flow in an adaptive context, however, have largely been equivocal, with examples of opposing outcomes being repeatedly documented (e.g., local adaptation with high levels of gene flow vs. gene swamping). We compared neutral genomic and venom expression divergence for three sympatric pit vipers with differing ecologies to determine if and how migration-selection disequilibria result in local adaptation. We specifically tested whether neutral differentiation predicted phenotypic differentiation within an isolation-by-distance framework. The decoupling of neutral and phenotypic differentiation would indicate selection led to adaptive divergence irrespective of migration, whereas a significant relationship between neutral and venom expression differentiation would provide evidence in favor of the constraining force of gene flow. Neutral differentiation and geographic distance predicted phenotypic differentiation only in the generalist species, indicating that selection was the predominant mechanism in the migration-selection balance underlying adaptive venom evolution in both specialists. Dispersal is thought to be a stronger influence on genetic differentiation than specialization, but our results suggest the opposite. Greater specialization may lead to greater diversification rates, and extreme spatial and temporal variation in selective pressures can favor generalist phenotypes evolving under strong stabilizing selection. Our results are consistent with these expectations, suggesting that the equivocal findings of studies examining the role of gene flow in an adaptive context may be explained by ecological specialization theory.

A spatial genomic approach identifies time lags and historical barriers to gene flow in a rapidly fragmenting Appalachian landscape.

The resolution offered by genomic data sets coupled with recently developed spatially informed analyses are allowing researchers to quantify population structure at increasingly fine temporal and spatial scales. However, both empirical research and conservation measures have been limited by questions regarding the impacts of data set size, data quality thresholds and the timescale at which barriers to gene flow become detectable. Here, we used restriction site associated DNA sequencing to generate a 2,140 single nucleotide polymorphism (SNP) data set for the copperhead snake (Agkistrodon contortrix) and address the population genomic impacts of recent and widespread landscape modification across an ~1,000-km2 region of eastern Kentucky, USA. Nonspatial population-based assignment and clustering methods supported little to no population structure. However, using individual-based spatial autocorrelation approaches we found evidence for genetic structuring which closely follows the path of a historically important highway which experienced high traffic volumes from c. 1920 to 1970 before losing most traffic to a newly constructed alternative route. We found no similar spatial genomic signatures associated with more recently constructed highways or surface mining activity, although a time lag effect may be responsible for the lack of any emergent spatial genetic patterns. Subsampling of our SNP data set suggested that similar results could be obtained with as few as 250 SNPs, and a range of thresholds for missing data exhibited limited impacts on the spatial patterns we detected. While we were not able to estimate relative effects of land uses or precise time lags, our findings highlight the importance of temporal factors in landscape genetics approaches, and suggest the potential advantages of genomic data sets and fine-scale, spatially informed approaches for quantifying subtle genetic patterns in temporally complex landscapes.

Obtaining plasma to measure baseline corticosterone concentrations in reptiles: How quick is quick enough?

There is growing interest in the use of glucocorticoid (GC) hormones to understand how wild animals respond to environmental challenges. Blood is the best medium for obtaining information about recent GC levels; however, obtaining blood requires restraint and can therefore be stressful and affect GC levels. There is a delay in GCs entering blood, and it is assumed that blood obtained within 3 min of first disturbing an animal reflects a baseline level of GCs, based largely on studies of birds and mammals. Here we present data on the timing of changes in the principle reptile GC, corticosterone (CORT), in four reptile species for which blood was taken within a range of times 11 min or less after first disturbance. Changes in CORT were observed in cottonmouths (Agkistrodon piscivorus; 4 min after first disturbance), rattlesnakes (Crotalus oreganus; 2 min 30 s), and rock iguanas (Cyclura cychlura; 2 min 44 s), but fence lizards (Sceloporus undulatus) did not exhibit a change within their 10-min sampling period. In both snake species, samples taken up to 3-7 min after CORT began to increase still had lower CORT concentrations than after exposure to a standard restraint stressor. The "3-min rule" appears broadly applicable as a guide for avoiding increases in plasma CORT due to handling and sampling in reptiles, but the time period in which to obtain true baseline CORT may need to be shorter in some species (rattlesnakes, rock iguanas), and may be unnecessarily limiting for others (cottonmouths, fence lizards).

Hemocoagulase agkistrodon can prevent bleeding and induce hypofibrinogenemia in hepatic disease cases
.

Hemocoagulase is often used for hemostasis in patients with bleeding and hemorrhagic diseases, and to avoid or stanch bleeding after surgery. Herein, three patients with hepatic diseases suffering from hypofibrinogenemia were treated with hemocoagulase agkistrodon (HCA) in Peking University People's Hospital during September 2018. All the 3 patients were chronic hepatitis B patients: Patient 1 presented with hepatic carcinoma and chronic hepatitis B, and right hepatectomy was performed; patient 2 presented with chronic hepatitis B and gastrointestinal bleeding; patient 3 presented with chronic hepatitis B, acute liver failure with hematemesis, and was awaiting liver transplantation. All three patients were percutaneously injected with HCA to prevent late-onset bleeding. After HCA was discontinued, coagulation was restored to > 60 mg/dL on day 6, without injection of fibrinogen. HCA significantly reduced the need for fibrinogen in patients with hepatic diseases, and the level of fibrinogen should be carefully monitored in clinical applications.

Fatal and Nonfatal Snakebite Injuries Reported in the United States.

OBJECTIVES: Venomous and nonvenomous snakes are found throughout the United States. Two families of venomous snakes are indigenous to this country: the Viperidae, or pit vipers (rattlesnakes, cottonmouths, and copperheads), and the Elapidae (three species of coral snakes and a sea snake). Bites from captive nonindigenous venomous snakes such as cobras also may present at medical facilities, given the interest in exotic pet ownership in the United States. Even "dry," nonenvenomating snakebites and those from nonvenomous snakes can result in puncture wounds that require medical evaluation. This article presents updated national estimates of snakebite injuries treated in US emergency departments (EDs). METHODS: Data on nonfatal snakebite injuries were abstracted from the National Electronic Injury Surveillance System-All Injury Program (2001-2015). Variables included age, sex, body part affected, cause, disposition, and treatment month. The snake species were coded based on narrative comments. Estimates were weighted and analyzed with SAS 9.4. Data on fatal snakebites were obtained from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiological Research (1999-2017). RESULTS: From 2001-2015, an estimated 137,800 snakebite injuries were treated in US EDs (crude rate: 3.0 individuals per 100,000 population). The majority of patients were male (70.7%; crude rate 4.4/100,000 population). Arms/hands (46.8%) and legs/feet (46.1%) were the primary body parts injured. The majority of patients were treated and released (67.1%); however, nearly 30% were hospitalized or transferred to another hospital. Two-thirds of the cases involved a nonvenomous or unknown snake (67.7%). Among venomous encounters, 70.3% involved a rattlesnake. For fatal snakebites, an average of 6 deaths per year was reported (range 2-12). CONCLUSIONS: Although rare, nonfatal snakebites in this study resulted in an estimated average of 9192 annual visits to EDs (roughly 1 visit per hour) and an average of 6 fatal snakebites per year. Epidemiologic data on snakebite injuries provide healthcare providers, public health officials, and veterinarians with information on populations at risk for snakebites, species of snakes likely to be encountered, and guidance for prevention efforts.

National Estimates of Noncanine Bite and Sting Injuries Treated in US Hospital Emergency Departments, 2011-2015.

OBJECTIVES: Injuries resulting from contact with animals are a significant public health concern. This study quantifies and updates nonfatal bite and sting injuries by noncanine sources using the most recent data available (2011-2015) from the National Electronic Injury Surveillance System-All Injury Program with the purpose of using these updates to better understand public health consequences and prevention techniques. Increased rates of bites and stings can be expected in this study's time frame, possibly caused by the increasing human population expanding into animal territories, as well as changes in animal geographic distribution and pet ownership. METHODS: The National Electronic Injury Surveillance System-All Injury Program is an ongoing nationally representative surveillance system used to monitor all types and causes of injuries treated in US hospital emergency departments (EDs). Cases were coded by trained hospital coders using information from medical records on animal sources of bite and sting injuries being treated. Data from 2011-2015 were weighted to produce national annualized estimates, percentages, and rates based on the US population. RESULTS: An estimated 1.17 million people visited EDs for noncanine bite and sting injuries annually. This translates to a rate of 371.3/100,000 people. Insects accounted for 71.0% of noncanine bite and sting injuries, followed by arachnids (19.2%) and mammals (7.8%). The estimated annual total lifetime medical and work cost of unintentional noncanine injuries was $5,755,581,000. CONCLUSIONS: Various sources of bite and sting injuries had an outsized effect on injury rates and identify potential areas of focus for education and prevention programs to reduce the burden of these injuries on health and healthcare costs. The study describes the diversity of animal exposures based on a national sample of EDs. Noncanine bite and sting injuries significantly affect public health and healthcare resources. Priorities can be focused on animal sources with the most impact on bite and sting injury rates, healthcare costs, and disease burden.

Purification and characterization of Protein C activator from Agkistrodon acutus Venom.

Protein C (PC) plays an important role in the balance of coagulation and anticoagulation. Thus, the detection of PC activity is diagnostically significant for patients with cardiovascular diseases. Presently, the key methods to detect PC activity are the chromogenic assay and activated partial thromboplastin time (APTT) test. PROTAC used in the chromogenic assay is isolated from Agkistrodon contortrix venom as protein C activator (PCA). However, the use of the chromogenic assay is limited because of the high price of PROTAC. In this study, PCA was successfully purified from Agkistrodon acutus venom (AAV) by ion-exchange and gel chromatography. PCA from AAV has a relative molecular mass of 24 kD, calculated from the measurement of 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The components of PCA were identified by MALDI-TOF/TOF-MS and mascot searches revealed that the coverage rate between PCA and zinc metalloproteinase AaPA from AAV was 21%. The chromogenic assay and APTT test were used to measure the enzymatic activity of PCA, and the results showed that PCA from AAV could specifically activate PC. In summary, the chromogenic assay described herein is highly sensitive and easy to perform.

Water relations of an insular pit viper.

Colonization of novel habitats often requires plasticity or adaptation to local conditions. There is a critical need to maintain hydration in terrestrial environments having limited water. Atypical populations of Florida cottonmouth snakes, Agkistrodon conanti, inhabit continental islands with no permanent sources of fresh water. Here, we report investigations related to how these insular snakes maintain water balance considering the mainland conspecifics are semi-aquatic and typically associate with freshwater mesic habitats. We tested three hypotheses related to water relations of insular populations of cottonmouth snakes compared with those on the mainland. (1) Voluntary drinking of fresh water in free-ranging insular snakes should reflect a relationship to recency of rainfall more strongly than in mainland snakes. (2) Insular snakes will tolerate greater dehydration before drinking than will mainland snakes. (3) Insular snakes will avoid drinking seawater more strongly than will those from the mainland. Between 2001 and 2018, we quantitatively estimated the hydration status of 337 individual cottonmouth snakes from insular populations and 30 cottonmouth snakes from mainland Florida, as judged by the tendency of wild-caught snakes to drink fresh water immediately following capture. We found that insular cottonmouth snakes had a higher incidence of dehydration than did mainland cottonmouth snakes (64% versus 23%), and the hydration status of the insular snakes correlated with patterns of precipitation. We also determined experimentally the dehydration threshold for drinking fresh water in insular (mean±s.d. -5.64±4.3%, n=34) and mainland cottonmouth snakes (-5.74±4.5%, n=21), and these were not significantly different. Discrimination tests for drinking serially from a graded series of brackish water showed that mainland snakes did not discriminate against the highest brackish value (10.5 ppt or 30% seawater), whereas insular snakes showed a preference for <15% seawater. Naive neonates from insular and mainland cohorts behaved similarly. The preference of insular snakes for fresh water represents an important aspect of the maintenance of water balance that differs from the mainland conspecifics and is likely a habituated or adaptive response to dependence on rainfall.

The extract from Agkistrodon halys venom protects against lipopolysaccharide (LPS)-induced myocardial injury.

BACKGROUND: Snake venoms contain various bioactive constituents which possess potential therapeutic effects. The aim of this work was to investigate the effect of the extract from Agkistrodon halys venom on lipopolysaccharide (LPS)-induced myocardial injury. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to three groups (10 rats per group): control group, LPS group and LPS + extract group. Rats in control and the LPS groups were intravenously injected with sterile saline solution, and rats in the LPS + extract group with the extract. After 2 h, rats of the control group were intraperitoneally injected sterile saline solution, and rats in the LPS and the LPS + extract groups were treated with LPS (20 mg per kg body weight). Levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum were determined. Anti-inflammation of the extract was analyzed via determination of TNF-α and IL-6 in serum, and expression of TNF-α, IL-6, COX-2 and p-ERK protein in hearts. Heme oxygenase-1 (HO-1) and p-NF-κB protein expression in hearts, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in serum were used to evaluate the anti-oxidative properties of the extract. RESULTS: Extract pretreatment significantly decreased the level of serum CK and LDH, reduced the generation of inflammatory cytokines such as TNF-α and IL-6, and also reduced serum level of MDA in the LPS + extract group compared with the LPS group. In addition, the extract increased SOD activity in serum, HO-1 protein expression in hearts, and decreased TNF-α, IL-6, COX-2, p-NF-κB and p-ERK1/2 protein expression. CONCLUSION: Our results suggested that beneficial effect of this extract might be associated with an improved anti-oxidation and anti-inflammatory effect via downregulation of NF-κB/COX-2 signaling by activating HO-1/CO in hearts.

Presumed Copperhead Snakebite and Antivenom Administration in the Third Trimester.

Snake envenomation during pregnancy is an uncommon emergency with several potential complications associated with the poisoning and its treatment. This case discusses a 27-y-old gravida 3, para 1102 (3 total pregnancies, 1 term birth, 1 premature birth, 0 abortions, 2 living births, twins) at 36 wk gestation who was bitten by a presumed Agkistrodon contortrix (copperhead snake). She had worsening pain and swelling in the right lower limb. Crotalidae polyvalent immune Fab was administered. The patient felt significantly better with improvement in swelling. She had a reactive nonstress test and reassuring coagulation studies. She gave birth to a healthy female infant 12 d later. This case supports the use of Crotalidae polyvalent immune Fab for venomous snakebites in pregnant patients to prevent possible maternal and fetal morbidity and mortality.

Current Management of Copperhead Snakebites in Missouri.

The past two decades have seen changes to the management of copperhead snakebites. We review the current use of antivenom, analgesics, and laboratory testing as well as the declining role of surgical management.